Variant 9-134882582-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004108.3(FCN2):c.157C>A(p.Pro53Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

FCN2
NM_004108.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25

Variant links:

Genes affected

FCN2 (HGNC:3624): (ficolin 2) The product of this gene belongs to the ficolin family of proteins. This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. This gene is predominantly expressed in the liver, and has been shown to have carbohydrate binding and opsonic activities. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FCN2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3 linkuse as main transcript	c.157C>A	p.Pro53Thr	missense_variant	2/8	ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	XM_011518392.4 linkuse as main transcript	c.124C>A	p.Pro42Thr	missense_variant	2/8		XP_011516694.1
FCN2	NM_015837.3 linkuse as main transcript	c.101-720C>A		intron_variant			NP_056652.1	Q15485-2
FCN2	XM_006717015.5 linkuse as main transcript	c.68-720C>A		intron_variant			XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 linkuse as main transcript	c.157C>A	p.Pro53Thr	missense_variant	2/8	1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 linkuse as main transcript	c.101-720C>A		intron_variant		5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251392

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.157C>A (p.P53T) alteration is located in exon 2 (coding exon 2) of the FCN2 gene. This alteration results from a C to A substitution at nucleotide position 157, causing the proline (P) at amino acid position 53 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.056

MetaRNN

Uncertain

0.56

MetaSVM

Pathogenic

0.89

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-6.5

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0050

Polyphen

0.93

Vest4

0.44

MutPred

0.67

Gain of phosphorylation at P53 (P = 0.0146);

MVP

0.95

MPC

0.44

ClinPred

0.97

GERP RS

3.9

Varity_R

0.61

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over